Spinal Cord Stimulation Prevents Progressive Motor Deterioration in an α-Synuclein-Based Rat Parkinson’s Disease Model

Spinal cord stimulation is a functional neurosurgery proposed for treating motor symptoms in patients with Parkinson’s disease, yet the mechanisms underlying motor symptom relief have not been elucidated. While preclinical studies suggest that long-term motor improvements may be due to neuroprotection of the nigrostriatal pathway, this evidence is limited to neurotoxic models. To evaluate the effect of spinal cord stimulation on nigrostriatal pathway neuroprotection in a genetic model of Parkinson’s disease, male Sprague-Dawley rats were unilaterally injected into the substantia nigra with empty or α-synuclein-coding adeno-associated viruses. Thirty-two days later, the rats were treated with 300 Hz spinal cord stimulation for ten weeks (two sessions/week). Ninety-one days post-injection treated α-synuclein rats had better motor performance than the untreated group, and no differences compared to the control group. However, spinal cord stimulation could not counteract the loss of dopaminergic neurons in the nigrostriatal pathway and did not cause changes in the total dopamine levels in the striatum, dopamine transporter, or tyrosine hydroxylase expression in the substantia nigra. The current study suggests that spinal cord stimulation prevents motor impairment in a genetic model of PD through a mechanism independent of the nigrostriatal pathway degeneration induced by α-synuclein overexpression.